Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.

Anti-Citrullinated Protein Antibodies (ACPA) in Unaffected Siblings of ACPA-Positive Rheumatoid Arthritis Patients.

Barra1,  Lillian, Wilson1,  Elizabeth, Scinocca1,  Matthias, Summers1,  Kelly, Cairns2,  Ewa, Bell2,  David A.

The University of Western Ontario
The University of Western Ontario, London, ON, Canada


We have previously reported that ACPA purified from RA patients injected intra-peritoneally (ip) into FcgRIIB-deficient mice induced inflammatory arthritis; whereas, ip injections of IgG devoid of ACPA from the same RA patients did not. ACPA has been shown to be positive in some unaffected first degree relatives of patients with RA (approximately 2% prevalence in a predominantly Caucasian population and 17% in a North American Native population) and its prevalence increases with the presence of the shared epitope (SE).


To determine whether unaffected siblings of ACPA positive RA probands have RA features and whether their ACPA can induce inflammatory arthritis experimentally.


Patients were included if they met ACR criteria for RA, had IgG anti-CCP2>50 and had unaffected siblings (confirmed after assessment by a physician). A questionnaire detailing medical history and risk factors for RA was completed. ACPA was affinity purified using a proprietary synthetic citrullinated peptide (JED) and administered ip to pre-autoimmune FcgRIIb deficient mice. IgG and IgM anti-JED and anti-CCP2 were measured by ELISA. All subjects were tested for the presence of the SE; levels of 27 cytokines were determined by Luminex®.


Twelve families were recruited for a total of 33 siblings (32 were unaffected with RA); there were two monozygotic twins discordant for RA. All subjects were Caucasian. Mean age of RA probands was 60, mean age of disease onset was 44, 10/12 (83%) were smokers, and 10/12 (83%) were in complete remission. Mean age of siblings was 51 and 14/29 (48%) were smokers, which was significantly less than RA probands (p=0.024). 9/12 probands were also IgG anti-JED positive and 7/12 were IgM anti-JED positive. One sibling was IgG anti-JED and anti-CCP2 positive. 10/31 siblings were IgM anti-JED positive; whereas, all normals (n=9) were negative. The monozygotic twins were also discordant for the presence of anti-JED and anti-CCP2. The results of HLA-typing and ip ACPA transfers are pending. Pro-inflammatory cytokines were elevated in RA patients compared to siblings and normals (p<0.05). Siblings did not have higher levels of pro-inflammatory cytokines than normals; however, the levels in smokers were higher than non-smokers (p<0.05).


Siblings of IgG anti-CCP2 postive RA probands had an increase in IgM anti-JED, but rarely had IgG anti-JED and IgG anti-CCP2 and also lacked elevation of pro-inflammatory cytokines characteristic of RA. Interestingly, monozygotic twins discordant for RA were also discordant for the presence of anti-CCP2 and anti-JED antibodies. Future work aims to determine whether IgM and IgG anti-JED isolated from these unaffected siblings is pathogenic in a mouse model of inflammatory arthritis.

To cite this abstract, please use the following information:
Barra, Lillian, Wilson, Elizabeth, Scinocca, Matthias, Summers, Kelly, Cairns, Ewa, Bell, David A.; Anti-Citrullinated Protein Antibodies (ACPA) in Unaffected Siblings of ACPA-Positive Rheumatoid Arthritis Patients. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1071
DOI: 10.1002/art.28838

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